The purpose of the proposed research is to define several parameters of cell-mediated immunity during cytomegalovirus (CMV) infection, i.e., CMV infection in renal transplant recipients. Previous studies from this laboratory have shown a selective lymphocyte hyporesponse during acute CMV mononucleosis to certain mitogens and CMV antigen (uptake of 3H-thymidine, interferon production). The reactivity to mitogens was greatly enhanced by preculturing of the cells for 1 or 7 days prior to mitogen stimulation. The proposed studies will separate B, T, and null lymphocytes from acute and convalescent CMV mononucleosis patients using cell rosetting techniques and define their response to mitogens and antigens using fresh and precultured cells. The presence of CMV in the cells will also be determined by cocultivation with human fibroblasts. The role of suppressor cells (adherent cells, T lymphocytes) in the lymphocyte hyporesponse and preculturing effect will be examined by cell depletion and reconstruction studies, as well as by studying CMV infection in blood monocytes. Soluble suppressor activity will be delineated by incubating cells from normal donors with patients' sera and supernatants from precultured cells. We will also prospectively analyze the mitogen and CMV antigen reactivity of lymphocytes from CMV-infected renal transplant recipients and the effect of preculturing on this response. This reactivity will be compared with the type of CMV infection, humoral immune response to CMV, immunosuppressive therapy, and frequency of superinfection in the patients.